e16136 Background: Gastric cancer (GC) is one of the most common cancers and a leading cause of cancer mortality. A diverse community of microorganisms is present in the human stomach and the host-microbe interactions contribute to carcinogenesis and progression of GC. Streptococcus anginosus (SA) was enriched in the gastric mucosa of patients with GC and may promote gastric inflammation, atrophy, and tumorigenesis. However, the potential mechanism is still not fully revealed. Methods: In this work, multi-omics including microbiome, transcriptome, and metabolome data combined with in vivo and in vitro studies were conducted to investigate the potential role and mechanism of SA in process of GC. Results: We analyzed the gastric microbiota of paired tumoral, peritumoral and normal tissues obtained from 144 GC patients by16S rRNA sequencing. SA was enriched stepwise in the normal, peritumoral and tumoral tissues. High level enrichment of SA in tumoral tissue showed poorer prognosis than low level group based on Kaplan-Meier analysis. We isolated and cultured SA from GC tissue, and GC cells co-cultured with SA or treated with SA metabolites enhanced cell proliferation, colony formation, migration and invasion abilities. SA also promoted tumor proliferation in vivo based on mouse transplanted tumor model. Metabolomic analysis showed the elevated level of 2-picolinic acid after treated with SA. We verified the promotional role of 2-picolinic acid on cell proliferation, colony formation and migration in vitro. Conclusions: Thus, this study demonstrated that SA plays significant roles in the progression of GC, and its metabolite, 2-picolinic acid, maybe the key factor in host-microbe interactions.

Gastric cancer (GC) remains a leading cause of cancer-related mortality globally and is characterized by significant inter- and intra-tumoral heterogeneity, which poses major challenges to effective treatment. Although traditional “one-size-fits-all” chemotherapy regimens have improved outcomes, the prognosis for advanced disease remains poor, necessitating a paradigm shift towards personalized medicine. This review provides a comprehensive synthesis of the current landscape of precision oncology in GC. We systematically analyze the clinical implications of major molecular classification systems, particularly The Cancer Genome Atlas (TCGA) subtypes (EBV-positive, MSI-H, GS, and CIN), and their role in guiding therapeutic stratification. The integration of molecular profiling has revolutionized the management of GC. We discuss the evolution of targeted therapies, ranging from established standards, like HER2 inhibition, to emerging targets, including Claudin18.2 and FGFR2, highlighting their potential of overcoming resistance mechanisms. Furthermore, we evaluate the efficacy of immune checkpoint inhibitors (PD-1/PD-L1 blockade), specifically in the context of high microsatellite instability (MSI-H) and EBV-positive subtypes, where these have demonstrated robust antitumor activity. Beyond tissue-based markers, this article also explores the expanding role of liquid biopsies, including circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA), as non-invasive tools for real-time monitoring of disease progression and therapeutic response. Precision oncology represents a transformative approach in GC, moving beyond histology to a molecularly driven treatment framework. However, realizing its full potential requires addressing challenges related to tumor heterogeneity and drug resistance. Future research must focus on validating novel biomarkers and developing synergistic combination strategies to further improve patient survival.

Acute pancreatitis (AP) is characterized by acinar cell injury and death triggered by multiple etiologies, culminating in local and systemic inflammatory responses. Current therapeutic options for AP, particularly severe AP, remain limited. While RIPK3-mediated necroptosis in pancreatic acinar cells has been implicated in AP pathogenesis, here we uncover an indispensable role for macrophage RIPK3 in driving AP-associated inflammation. We find that RIPK3 expression is progressively upregulated during AP progression. In cerulein-induced AP, both pharmacological RIPK3 inhibition and macrophage-specific Ripk3 deletion attenuate pancreatic injury, whereas Mlkl deletion in macrophages has no effect. Macrophage-specific RIPK3 knockout also reduces systemic inflammation and improves survival in the severe AP (NaTc-SAP) mouse model. After LPS activation, RIPK3-deficient macrophages exhibit impaired inflammatory responses and reduced NF-κB and MAPK activation. Mechanistically, RIPK3 interacts with TRAF6 to promote its K63-linked ubiquitination. These findings establish macrophage RIPK3 as a key mediator of AP and highlight its potential as a therapeutic target.

BACKGROUND Gastric cancer (GC) remains a leading cause of cancer mortality worldwide. Despite improved survival with surgery combined with chemotherapy and immunotherapy, these treatments frequently induce gastrointestinal mucosal injury and disrupt intestinal microecological homeostasis, resulting in severe dysbiosis. Premna microphylla Turcz. (PMT), a traditional medicinal and edible herb, exhibits anti-inflammatory and immunomodulatory properties. However, the metabolism of PMT bioactive components in a compromised intestinal microenvironment and their roles in microecology-mediated intestinal repair remain poorly understood. AIM To establish a Simulator of the Human Intestinal Microbial Ecosystem (SHIME) model for explicitly elucidating the segment-specific metabolism of PMT. METHODS Using the SHIME model, this study simulated the absorption of PMT in GC patients undergoing chemotherapy and immunotherapy, aiming to clarify its active components' intestinal recovery mechanism and nutritional intervention value. RESULTS Components of PMT were converted into small-molecule phenolic acids by microbiota. Their absorption and metabolism showed heterogeneity and dynamics across intestinal segments, e.g ., flavonoid glycosides are activated rapidly in the small intestine, while hydrophobic terpenes are retained in the colon. The shifted primary absorption site in the intervention group (e.g ., epicatechin from the small intestine in the control group to the colon in the treatment group) suggests that dysbiosis may reshape drug absorption pathways, providing a theoretical basis for natural nutrient-based nutritional strategies for cancer patients. CONCLUSION The SHIME model revealed PMT’s metabolism-repair dual pathway in chemotherapy and immunotherapy-damaged intestines, laying a theoretical foundation for its targeted nutritional rehabilitation strategies for cancer patients’ intestinal microecology.

Background: Neoadjuvant chemotherapy (NAC) is recommended to improve the resection rate and reduce mortality in patients with locally advanced gastric cancer (LAGC). However, tumor heterogeneity causes diverse pathological responses to NAC. Identifying pathological responses prior to treatment is clinically important but remains challenging. This study aimed to explore the predictive capacity of integrating radiomics and pathomics features for predicting pathological responses to NAC in LAGC patients, using pre-treatment contrast-enhanced CT images and biopsy hematoxylin and eosin-stained whole slide images (WSIs). Methods: We retrospectively recruited 146 eligible patients with available pre-treatment contrast-enhanced CT images and WSIs. The radiomics and pathomics features, extracted from CT images and WSIs, were integrated to construct the multi-omics prediction model to predict the pathological responses (good response, GR; moderate response, MR; and poor response, PR) to NAC by the eXtreme Gradient Boosting algorithm in the training cohort. Additionally, three single-omics prediction models-the radiomics, pathomics, and clinical models-were constructed based on radiomics, pathomics, and clinical features, respectively. The accuracy and robustness of the models were evaluated and compared in both internal and external validation cohorts. The prognostic value of the multi-omics model was further explored using the Kaplan-Meier method and Cox proportional hazards regression model. Results: The multi-omics model had favorable performance in predicting pathological responses to NAC with the areas under the receiver operating characteristic curve (AUCs) of 0.935 (95% CI, 0.909-0.961), 0.882 (95% CI, 0.792-0.973), and 0.836 (95% CI, 0.715-0.957) in the training, internal validation, and external validation cohorts which outperformed single-omics prediction models. Furthermore, the multi-omics model's prediction was significantly correlated with 2-year disease-free survival probabilities and identified as an independent prognostic factor for LAGC patients. (MR vs GR, hazard ratio [HR] = 2.60 (95% CI, 1.10-5.90); PR vs GR, HR = 2.90 (95% CI, 1.20-6.90)). Conclusions: Our study provides a feasible rationale for integrating the multi-omics features to improve the prediction of pathological responses in patients with LAGC. The multi-omics model is promising to assist clinicians in predicting pathological responses to NAC for LAGC patients and formulating personalized neoadjuvant therapies before treatment.

Hiatal hernia (HH), a common digestive disease, may impact the respiratory system, but systematic evaluation of its effect on cardiopulmonary function and associations with clinical indicators remains insufficient. This retrospective study included 248 HH patients (118 surgical [SHH], 130 non-surgical [NHH]) and 516 healthy controls (HC) from The First Affiliated Hospital of Zhejiang University School of Medicine (January 2021–December 2024). Data on basic information, imaging, pulmonary function, echocardiography, and reflux symptoms were collected. Differences in cardiopulmonary function among groups were compared through multi-factor adjustment analysis, and related influencing factors were explored. HH patients had higher pulmonary infection risk, poorer ventilatory/small airway/diffusing function, and wider pulmonary artery (PA) diameter. NHH patients were older, had larger hernia sacs, and worse cardiopulmonary function but fewer reflux symptoms. The differences in cardiopulmonary function among the above groups weakened after excluding confounding factors such as age. Advanced age and large hernia sac (not reflux) correlated with impaired cardiopulmonary function. 81.2

e16047 Background: Grim prognosis and medical scarcities of gastric cancer (GC) with liver metastasis (LM) presents the significant challenge. Chemotherapy plus programmed cell death inhibitors provided promising opportunities to solve such problems and the dedicated trail is warranted. Methods: In this prospective, single-arm phase 2 trail, untreated synchronous GC-LM are eligible and receive SOX plus Tisleizumab (200mg, Q3W) for 8 cycles, maintenance therapy is S-1 within 1 year plus Tisleizumab within 2 years, or until disease progression. The primary endpoint was objective response rate (ORR), secondary endpoints included disease control rate (DCR), progression-free survival (PFS) and overall survival (OS). This exploratory study hypothesized chemotherapy plus tislelizumab would increase ORR from 25% to 56%, with one-sided α of 0.05, statistical power of 0.8, considering 10% dropout, 33 patients are required. Results: 34 patients were enrolled and 4 patients were excluded from efficacy analysis (3 withdrawal of consent, 1 loss to follow-up). Median follow-up was 24.00m (14.18-33.82, 95%CI). ORR is 73.33% (22/30) and DCR is 86.67% (26/30). Median PFS and OS is 21.00m (14.13-27.87) and 24.00m (14.18-33.82). Mean maximal tumor volume regression of GC is 36.17% and the time to reach maximal tumor regression is 3.5m, correspondingly, 46.67% and 3.87m are observed in LM. 33.33% (10/30) patients received conversion surgery (CS) and TRG0 ratio is 16.67% (5/30). CS has significantly better median OS (P = 0.004) and median PFS/DFS (P = 0.005). Conclusions: Chemotherapy (SOX) plus Tisleizumab as first line treatment of GC-LM demonstrated clinically meaningful benefits in both treatment response and prolonged survival. Particularly, increased CS rate provided additional survival benefits. Clinical trial information: NCT05325528 . N MedianOS (95% CI) P-value MedianPFS (95% CI) P-value All patients 30 Age ≥65 18 28.00 (NR-NR) 0.129 21 (NR-NR) 0.273 ＜65 12 20.00 (NR-NR) 16.00 (NR-NR) Sex Female 3 28.00 (10.17-45.83) 0.526 17.00 (NR-NR) 0.525 Male 27 24.00 (NR-NR) 21.00 (1.37-40.63) N stage N1-2 18 24.00 (NR-NR) 0.710 17.00 (NR-34.31) 0.736 N3a&b 12 28.00 (NR-NR) 21.00 (NR-NR) Gastric tumor diameter<5cm 14 32.48 (NR-NR) 0.068 NR 0.012 diameter≥5cm 16 12.00 (NR-25.28) 4 (NR-18.00) Liver metastasis Unilobar 13 NR (NR-NR) 0.045 NR 0.112 Multilobar 17 20.00 (4.65-35.35) 16.00 (.446-31.55) Tumor number <5 15 20.00 (4.461-35.54) 0.082 NR 0.188 Tumor number ≥5 15 NR (NR-NR) 17.00 (.83-33.17) Maximal tumor diameter<5cm 17 NR (NR-NR) 0.006 27.00 (NR-NR) 0.014 Maximal tumordiameter≥5cm 13 20.00 (3.10-36.89) 16 (NR-34.79) PD-L Negative 13 12.00 (3.39-26.26) 0.407 18.28 (0.00-36.15) 0.654 ≥1 17 28.00 (12.89-43.11) 23.00 (NR-NR) Conversion surgery Yes 10 NR 0.004 NR 0.005 No 20 20.00 (1.19-41.81) 16.00 (0.00-38.99) Recist PR+CR 22 28.00 (NR-NR) 0.001 NR (NR-NR) 0.000 SD+PD 8 5.00 (2.44-7.56) 1.13 (NR)

BACKGROUND:Gastric cancer (GC) patients often have nutritional risks or malnutrition, and neoadjuvant chemotherapy (NAC) tends to exacerbate malnutrition. Body composition parameters are associated with the prognosis of GC patients. Little is known about body composition changes during NAC and its role in clinical outcomes. METHODS:This was a secondary analysis of a Phase 3, open-label, multicentre, randomized clinical trial (RCT) (NCT01364376), assessing the usefulness, safety and efficacy of S-1 plus oxaliplatin (SOX) vs. fluorouracil, leucovorin and oxaliplatin (FOLFOX) as a perioperative chemotherapy regimen for patients with locally advanced GC. Pre-NAC and post-NAC computer tomography (CT) were collected to evaluate the prognostic role of skeletal muscle, adipose tissue and their dynamic change. Overall survival (OS) and progression-free survival (PFS) rates were calculated using the Kaplan-Meier method. RESULTS:A total of 583 patients from 12 Chinese hospitals were enrolled. After exclusion, 423 patients who proceeded to surgery were used for further analysis. The median age was 60 (IQR: 54, 66) years, and 133 patients (31.4%) were female. Prior to NAC, 132 (31.2%) patients were diagnosed with sarcopenia. There was no significant difference in overall survival between sarcopenia and non-sarcopenia patients (p = 0.363). During NAC, most patients suffered skeletal muscle (SM) loss (n = 268, 63.4%), subcutaneous adipose tissue (SAT) loss (n = 236, 55.8%) and visceral adipose tissue (VAT) loss (n = 254, 60.0%). Patients with SAT loss > 12.5% had significantly worse PFS (p = 0.005) and OS (p = 0.003) than those without. Patients with VAT loss > 15% had significantly worse PFS (p = 0.003) and OS (p = 0.004) than the stable or gain group. Patients with SMI loss > 4.7% had significantly worse PFS (p = 0.043) and showed a tendency of reduced OS (p = 0.181) than those without. In patients without sarcopenia, the incidence of grade 3/4 neutropenia in the FOLFOX group was higher than that of the SOX group (p = 0.019). In patients with myosteatosis, the incidence of Grade 3/4 thrombocytopenia in the SOX group was higher than that of the FOLFOX group (p < 0.001). CONCLUSION:In this RCT study, patients with GC experience significant losses of muscle and adipose tissue during NAC. A high level of adipose tissue or muscle loss during NAC is prognostic of reduced survival in patients with locally advanced GC. Assessing and monitoring body composition can predict prognosis and effectively guide individual nutrition intervention and the prevention of complications.

Background:Immune checkpoint inhibitors have shown promising results in the treatment of advanced gastric or gastroesophageal junction (G/GEJ) adenocarcinoma. Objectives:To evaluate the safety and efficacy of camrelizumab combined with S-1 plus oxaliplatin chemotherapy in the postoperative setting for pathological stage III (pStage III) G/GEJ adenocarcinoma. Design:This study was a prospective, multicenter, single-arm, phase II trial. Methods:Patients with pStage III G/GEJ adenocarcinoma were enrolled, receiving camrelizumab (200 mg), followed by oxaliplatin (130 mg/m2), both administered on day 1 of each 21-day cycle, and tegafur-gimeracil-oteracil potassium capsules (40-60 mg, twice daily) for 2 weeks, followed by a 7-day rest period. A total of eight treatment cycles were planned. The primary endpoints were the incidence of any-grade and grade 3 or 4 adverse events. The secondary endpoints were disease-free survival (DFS), overall survival (OS), and treatment completion rate. Results:Between September 2020 and March 2023, 52 patients were enrolled at three medical centers in Zhejiang Province, China. All 52 patients (100%) experienced treatment-related adverse events (TRAEs). Grade 3 or higher TRAEs were reported in 35 patients (67.3%). Events occurring in >10% of the patients included decreased neutrophil count, neutropenia, leukopenia, thrombocytopenia, and anemia. Eleven (21.2%) patients experienced TRAEs that led to the interruption or discontinuation of camrelizumab, including rash (1), hypothyroidism (1), hyperkalemia (1), interstitial pneumonia (2), cystitis or urethritis (2), and reactive cutaneous capillary endothelial proliferation (4). The actual 2-year DFS and OS rates were 82.4% and 86.3%, respectively, whereas the estimated 3-year DFS and OS rates were 69.1% and 71.3%, respectively. Conclusion:Camrelizumab combined with chemotherapy has a manageable and tolerable safety profile as an adjuvant treatment for pStage III G/GEJ adenocarcinoma. However, careful patient selection is necessary to identify patients most likely to benefit from combination therapy. Trial registration:ClinicalTrials.gov registry: NCT04515615; Date of registration: August 14, 2020; Weblink: https://clinicaltrials.gov/study/NCT04515615.

Introduction: Gastrointestinal stromal tumors (GISTs) are primarily driven by mutations in KIT (KIT proto-oncogene receptor tyrosine kinase) or PDGFRA (platelet-derived growth factor receptor alpha), but resistance to tyrosine kinase inhibitors (TKIs) such as imatinib remains a major clinical challenge. Alterations in fibroblast growth factor receptor 2 (FGFR2), although rare, are emerging as important contributors to tumor progression and drug resistance. This review evaluates the molecular mechanisms, expression profiles, detection methods, and therapeutic implications of FGFR2 in GIST. Methods: We searched PubMed, Web of Science, Google Scholar, and ClinicalTrials.gov for studies published between January 2010 and June 2025, using combinations of keywords related to FGFR2, gastrointestinal stromal tumor, resistance mechanisms, gene fusion, amplification, polymorphisms, and targeted therapy. Eligible studies were critically assessed to distinguish GIST-specific data from evidence extrapolated from other cancers. Results:FGFR2 is expressed in multiple normal tissues and at variable levels in mesenchymal-derived tumors, including GIST. Its alterations occur in approximately 1–2% of GIST cases, most commonly as gene fusions (e.g., FGFR2::TACC2, <1%) or amplifications (1–2%); point mutations and clinically significant polymorphisms are extremely rare. These alterations activate the MAPK/ERK and PI3K/AKT pathways, contribute to bypass signaling, and enhance DNA damage repair, thereby promoting TKI resistance. Beyond mutations, mechanisms such as amplification, ligand overexpression, and microenvironmental interactions also play roles. FGFR2 alterations appear mutually exclusive with KIT/PDGFRA mutations but occasional co-occurrence has been reported. Current clinical evidence is largely limited to small cohorts, basket trials, or case reports. Conclusions:FGFR2 is an emerging oncogenic driver and biomarker of resistance in a rare subset of GISTs. Although direct evidence remains limited, particularly regarding DNA repair and polymorphisms, FGFR2-targeted therapies (e.g., erdafitinib, pemigatinib) show potential, especially in combination with TKIs or DNA-damaging agents. Future research should prioritize GIST-specific clinical trials, the development of FGFR2-driven models, and standardized molecular diagnostics to validate FGFR2 as a therapeutic target.

A 77-year-old woman presented to the emergency department with a 2-day history of abdominal distension, pain, nausea and inability to pass stools or flatus. Her medical history included hypertension, coronary heart disease, and cerebral infarction. She had undergone a laparotomy for intestinal obstruction at age 11 years and had experienced similar episodes of pain monthly over the past 66 years, which were usually relieved with conservative treatment. A computed tomography (CT) scan revealed a dilated small bowel with cluster of concretions (Fig. 1). The patient had no history of pica and no signs of a biliary-enteric fistula or gas in the bile duct were observed. Nasogastric suction and intravenous fluids were administered. After a 10-day conservative treatment, the patient continued to experience abdominal distension. Exploratory laparotomy a section of small bowel 2 m from the ligament of Treitz with oedema, thickening and fibrosis. Segmental small bowel resection and primary anastomosis were performed. Upon opening the resected bowel, a cluster of cobblestones were found (Fig. 2). Pathological examination revealed intestinal wall congestion, stasis, and shrinkage or degeneration of the smooth muscle. Further analysis of the enteroliths using liquid chromatograph-mass spectrometer (LC–MS) demonstrated cholic acid and deoxycholic acid as the main organic components (Fig. 3), and calcium as the predominant metallic inorganic component using inductively coupled plasma-mass spectrometry (ICP-MS). The patient was discharged after 10 days and remained symptom-free at subsequent telephone follow-up. Enterolithiasis in the gastrointestinal tract is relatively rare, with a reported prevalence of 0.3–10%.1 It is often associated with intestinal abnormalities, such as diverticula, prior surgery, radiation enteritis and chronic inflammation, which can reduce bowel motility and promote elemental accumulation.1, 2 Enteroliths are classified into primary and secondary types. Primary enteroliths, which formed from materials normally present in chyme including choleic acid enteroliths, typically found in the proximal small bowel, and calcium salts enteroliths generally in the terminal ileum. Secondary enteroliths refer to the stone formed outside the gastrointestinal tract that migrate into the bowel, usually derived from gallstones or renal stones, such as cholecystoduodenal and biliary-enteric fistula.1, 3-5 The mortality rate for primary enterolithiasis is generally low but may reach 3% in cases of delayed diagnosis, poor health conditions, or severe obstruction.5, 6 In the present case, the obstruction may have resulted from post-surgery stricture-induced bowel stasis during the past 66 years, allowing cholic acid to gradually form enteroliths at the proximal jejunum. These stones subsequently migrated to the distal intestinal accompanied by calcium salt precipitation and bacterial overgrowth, resulting in deconjugation of bile salts and turning soluble cholic acid into insoluble deoxycholic acid. This transformation may account for cobblestone-like look of the enterolith. Optimal treatment involves eliminating the enteroliths and correcting the underlying pathology. The surgical treatment in this case was successful, and the patient remained symptom-free postoperatively. Written informed consent was obtained from the patient for the publication of this case and the accompanying images. Hailong Jin: Conceptualization; writing – original draft; writing – review and editing. Yongqiang Si: Methodology; resources; writing – review and editing. Xiaoyong Zhang: Formal analysis; methodology. Xiaosun Liu: Conceptualization; supervision; writing – review and editing.

BACKGROUND:To investigate the expression and associations of putative stem cell markers with survival in patients with locally advanced gastric cancer (GC) receiving neoadjuvant chemotherapy. METHODS:This study included 180 patients with locally advanced GC who received neoadjuvant chemotherapy and subsequent radical gastrectomy between June 2010 and December 2014. Surgical paraffin samples from the enrolled patients were collected. Tissue microarrays were used to detect the expression patterns of 10 putative stem cell markers; immunohistochemistry was used to evaluate the expression patterns of CD133 and SOX2 in GC and adjacent tissues. The prognostic values of these tumor markers for survival in GC were evaluated. RESULTS:Following adjustments for sex and age, high CD133 and SOX2 expression levels after neoadjuvant chemotherapy were associated with poor survival in GC patients (p = 0.012 and = 0.022, respectively). Subgroup analysis showed that CD133 and SOX2 expression levels in the T2-4 population after neoadjuvant chemotherapy were negatively associated with survival in GC patients (p = 0.017 and 0.036, respectively). The BAX expression level in the N0 population after neoadjuvant chemotherapy was positively associated with survival in GC patients (p = 0.045). In the N1+2+3 population, a higher E-cadherin expression level after neoadjuvant chemotherapy was associated with longer survival among GC patients (p = 0.006). CONCLUSIONS:The CD133 and SOX2 expression levels after neoadjuvant chemotherapy are independent predictors of survival in locally advanced GC patients receiving neoadjuvant chemotherapy, and higher CD133 and SOX2 expression levels were associated with lower mortality rates.

BACKGROUND In the management of diffuse large B-cell lymphoma (DLBCL), PET/CT imaging is routinely utilized after completion of 6-8 cycles of chemotherapy to assess therapeutic response. Lymph nodes displaying elevated 18F-Fluorodeoxyglucose (FDG) uptake on these scans frequently necessitate pathological verification or escalation of treatment intensity. While core-needle biopsy (CNB) is a widely used minimally invasive technique for lymph node sampling in superficial anatomical sites, its diagnostic yield for retroperitoneal lymph nodes remains suboptimal due to technical constraints, necessitating reliable diagnostic alternatives. Presently, standardized diagnostic algorithms are lacking for such metabolically active retroperitoneal lesions. CASE REPORT We prospectively evaluated 5 consecutive DLBCL patients with histologically confirmed diagnoses who completed 6-8 cycles of first-line immunochemotherapy. End-of-treatment PET/CT demonstrated metabolically active retroperitoneal lymph nodes (Deauville score 4-5) in all participants, meeting the criteria for equivocal treatment response. After excluding surgical contraindications, diagnostic laparoscopic retroperitoneal lymph node excision was performed under general anesthesia. The procedure successfully retrieved adequate tissue specimens from all targeted lesions, without intraoperative complications. Systematic histopathological evaluation incorporating immunohistochemical staining protocols was subsequently conducted on all specimens, revealing benign changes in 4 cases and residual lymphoma in 1 case. The resultant pathological profiles provided critical diagnostic clarity, directly informing subsequent therapeutic decision-making for each patient. CONCLUSIONS Laparoscopic lymph node excision constitutes a technically feasible and diagnostically robust approach for DLBCL patients with post-chemotherapy retroperitoneal FDG-avid lesions. This technique offers superior tissue acquisition capability compared to percutaneous biopsies, delivering essential pathological evidence to guide risk-adapted management strategies when conventional diagnostic modalities prove inconclusive.

Acute pancreatitis is a condition characterized by the injury and death of pancreatic acinar cells caused by multiple factors, ultimately leading to local or systemic inflammatory responses. Existing treatment methods for acute pancreatitis, especially severe acute pancreatitis, are still limited. Previous studies have shown that RIPK3 makes a prominent contribution to the regulation of pancreatic acinar cell necroptosis. In this study, our research has found that RIPK3 also plays an indispensable role in regulating the inflammatory response of macrophages. Studies have shown that the RIPK3 inhibitor GSK-872 and conditional knockout of RIPK3 in macrophages effectively alleviate pancreatic tissue damage. It is also elucidated that macrophage RIPK3 interacts with TRAF6, facilitates TRAF6-K63 ubiquitination, triggers the activation of the NF-κB and MPAK inflammatory signaling pathways, rather than through the necroptosis mechanism, and promotes the occurrence and development of acute pancreatitis. This study will focus on exploring the regulatory role and mechanism of RIPK3 in macrophages, providing new strategies and targets for the therapy of acute pancreatitis.

BACKGROUND:Gastrointestinal stromal tumors (GISTs) are generally characterized by driver mutations in KIT or PDGFRA. However, the molecular landscape of wild-type GISTs remains complex, posing significant therapeutic challenges. Recent evidence has indicated alterations in FGFR2 as potential oncogenic drivers in patients with various cancers. However, the role of these drivers in GIST pathogenesis remains underexplored. CASE SUMMARY:We retrospectively evaluated two patients with GIST, diagnosed between August 2021 and July 2022, harboring FGFR2 mutations through hybrid capture-based next-generation sequencing (NGS). We analyzed their clinicopathological characteristics, treatment response, and long-term follow-up data. Both patients, a 47-year-old man (case 1) and a 43-year-old woman (case 2), underwent successful surgical resection and received adjuvant imatinib therapy. They achieved sustained remission with a median follow-up of 28 months. Notably, the NGS revealed novel FGFR2 rearrangements, an FGFR2-CIT/intergenic-FGFR2 fusion in case 1 and FGFR2-CAMK2G/FGFR2-VCL fusions in case 2 without canonical KIT or PDGFRA mutations. Both patients exhibited a favorable response to standard imatinib treatment. CONCLUSION:Our findings provided preliminary evidence that novel FGFR2 fusions might act as primary oncogenic drivers in a rare subset of KIT/PDGFRA wild-type GISTs. These cases highlight the importance for comprehensive genomic profiling and suggest that fibroblast growth factor receptor-targeted inhibitors could be a potential therapeutic strategy for advanced or imatinib-resistant diseases, warranting further investigation in larger cohorts.

>To the Editor: Hepatic cavernous hemangiomas constitute 73%of all benign hepatic tumors,and large hemangiomas may protrude beyond the hepatic contour and exert compression on adjacent structures[1].The diagnosis of hepatic hemangioma is usually accidental,rarely related to symptoms,and most cases are diagnosed through ultrasound.Surgical treatment,including locoregional ablation techniques and radical intent,is advised for patients with symptomatic hemangioma[2,3].Gastrointestinal stromal tumor is a type of sarcoma primarily originating from the precursor of the interstitial

Over the past few years, there has been an increasing interest in investigating tumor-infiltrating lymphocytes. B lymphocytes (B cells) are extensively distributed within tertiary lymphoid structure (TLS) as multifaceted subgroups and are intimately linked to the anti-tumor properties of TLS, as well as the survival and prognostication of individuals. While the investigation of T lymphocytes in the TLS has advanced to the level of clinical practice, the study of B cells remains limited. The principal impediment to the utilization of B cells in immunotherapy is their notable dual impact on tumors. Compared with tumors in other parts and systems, the function of B cells in the microenvironment of digestive system tumors to promote tumors proliferation, differentiation and migration cannot be ignored. Therefore, this review collects the studies of B cell subsets in tumor microenvironments, particularly related single cell sequencing research. The multifaceted role and function of B cells are investigated in esophageal, liver, colorectal, gastric and pancreatic cancers. And through the identification of B cell subsets and specific markers, this review attempts to explain the reasons why B cells produce different tumor-promoting effects in those tumors. The insights gleaned from this review may provide potential help and support the development of B cell-based immunotherapies.

BackgroundGastric Cancer (GC) characteristically exhibits heterogeneous responses to treatment, particularly in relation to immuno plus chemo therapy, necessitating a precision medicine approach. This study is centered around delineating the cellular and molecular underpinnings of drug resistance in this context.MethodsWe undertook a comprehensive multi-omics exploration of postoperative tissues from GC patients undergoing the chemo and immuno-treatment regimen. Concurrently, an image deep learning model was developed to predict treatment responsiveness.ResultsOur initial findings associate apical membrane cells with resistance to fluorouracil and oxaliplatin, critical constituents of the therapy. Further investigation into this cell population shed light on substantial interactions with resident macrophages, underscoring the role of intercellular communication in shaping treatment resistance. Subsequent ligand-receptor analysis unveiled specific molecular dialogues, most notably TGFB1-HSPB1 and LTF-S100A14, offering insights into potential signaling pathways implicated in resistance. Our SVM model, incorporating these multi-omics and spatial data, demonstrated significant predictive power, with AUC values of 0.93 and 0.84 in the exploration and validation cohorts respectively. Hence, our results underscore the utility of multi-omics and spatial data in modeling treatment response.ConclusionOur integrative approach, amalgamating mIHC assays, feature extraction, and machine learning, successfully unraveled the complex cellular interplay underlying drug resistance. This robust predictive model may serve as a valuable tool for personalizing therapeutic strategies and enhancing treatment outcomes in gastric cancer.